Preparation of C-2-pyridyl derivatives of icosahedral carboranes via copper(I) intermediates

Gill, Wendy R.; Herbertson, Penelope L.; Macbride, J. A. H.; Wade, Kenneth

doi:10.1016/0022-328x(95)05742-8

Cited by 32 publications

(12 citation statements)

References 23 publications

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“…This meant that a bond had to be formed between the cluster and the vinyl carbon atom at the 3-position of the butenolide ring. Accordingly, a copper-catalyzed C-C coupling reaction with elevated temperatures and long reaction times was performed 43,44 . However, this approach did not yield the desired product, because the butenolide ring proved to be labile under the required basic conditions at elevated temperatures 45 .…”

Section: Resultsmentioning

confidence: 99%

Carboranyl Derivatives of Rofecoxib with Cytostatic Activity against Human Melanoma and Colon Cancer Cells

Buzharevski

Paskaš²,

Sárosi

et al. 2020

Sci Rep

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Owing to the involvement of cyclooxygenase-2 (COX-2) in carcinogenesis, COX-2-selective inhibitors are increasingly studied for their potential cytotoxic properties. Moreover, the incorporation of carboranes in structures of established anti-inflammatory drugs can improve the potency and metabolic stability of the inhibitors. Herein, we report the synthesis of carborane-containing derivatives of rofecoxib that display remarkable cytotoxic or cytostatic activity in the micromolar range with excellent selectivity for melanoma and colon cancer cell lines over normal cells. furthermore, it was shown that the carboranemodified derivatives of rofecoxib showed different modes of action that were dependent on the cell type. Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used therapeutics for the treatment of pain and inflammation 1. Their molecular target is the enzyme cyclooxygenase (COX), which catalyzes the dioxygenation/cyclization of arachidonic acid to form prostaglandin H2 (PGH2), which is further metabolized to prostaglandins (PGs), which in turn act as mediators of inflammation 2. The enzyme occurs as two isoforms: a constitutive one, namely COX-1, producing a basic level of PGs, and an inducible one, namely COX-2, activated by inflammatory stimuli 3. COX-2 expression is also upregulated in multiple human cancers 4,5. There is a substantial body of evidence that genetic deletion or pharmacological inhibition of COX-2 abrogates tumorigenesis 6-11. Thus, NSAIDs, in particular COX-2-selective inhibitors, have garnered attention as potential cytostatic drugs. For example, rofecoxib was shown to exhibit excellent potential as a cytotoxic agent 8,12-15. In addition to inhibition of COX, it was demonstrated that the cytotoxic activity of NSAIDs also involves the inhibition of other cellular targets. Unfortunately, the widespread use of COX-2-selective inhibitors revealed an increased risk for cardiovascular adverse effects in long-term therapy 16,17. This prompted research into the development of COX-2-selective inhibitors with improved cardiovascular safety profiles. One promising approach is the incorporation of nitric oxide (NO)-releasing moieties into the structures of COX inhibitors, given that NO has vasodilatory activity and inhibits platelet aggregation 18-22. Moreover, as NO plays an important role in the formation and progression of various cancers 23 , NO-releasing analogues of rofecoxib (Fig. 1) were evaluated for their cytotoxic potency. These compounds retained an inhibitory potential against COX-2 similar to that of rofecoxib but exhibited even higher cytotoxic activity 24,25. The highly dynamic field of drug design and synthesis is constantly in search of new pharmacophores. Recently, polyhedral heteroboranes, namely dicarba-closo-dodecaboranes (carboranes) 26 , have been increasingly studied as hydrophobic moieties 27,28. Carboranes are icosahedral clusters composed of ten BH and two CH vertices; different positions of the CH vertices give rise to ortho (1,2-), meta (1,7-), and...

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Section: Resultsmentioning

confidence: 99%

Carboranyl Derivatives of Rofecoxib with Cytostatic Activity against Human Melanoma and Colon Cancer Cells

Buzharevski

Paskaš²,

Sárosi

et al. 2020

Sci Rep

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“…Unlike the carboranyllithiums, the carboranylcopper reagents do not equilibrate with the C-H acid form and high degrees up to 80% of monoarylation of 6 have been obtained 13,82,92 . The original Wade procedure 76 for arylation of the twelve-vertex carboranes 13,82,92,93 has been extended to arylation 58,94 and ethynylation 23 of the ten-vertex para-carborane 10. Attempts to use the procedure for the introduction of perfluoroalkyl de- rivatives proved unsuccessful, and only carboranyl halides 28 (bromides and iodides) were obtained in the metal-halogen exchange process (Scheme 5) 82 .…”

Section: Carbon Substitutionmentioning

confidence: 99%

Four Decades of Organic Chemistry of closo-Boranes: A Synthetic Toolbox for Constructing Liquid Crystal Materials. A Review

Kaszyński

1999

Collect. Czech. Chem. Commun.

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Introduction and transformations of organic functional groups to ten- and twelve-vertex closo-boranes and heteroboranes is reviewed in the context of preparation of liquid crystalline compounds. The review, containing 198 references, is designed as a synthetic manual for materials chemists and focuses on methods for engineering molecules with elongated shapes and variable dipole moments. Several underdeveloped aspects of closo-borane chemistry are identified.

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“…To date, functionalization at the C atoms of carbaborane cages has led to numerous derivatives, and of particular interest to the present perspective is the connection of clusters into cyclic arrays: for example arene-coupled systems, [12] a related cyclic trimer formed by treatment of 2,6-Br 2 H 3 C 5 N with 1,7-Cu 2 -1,7-C 2 B 10 H 10 from Wade and co-workers, [13] and macrocycles such as 3 and 4 from the Hawthorne group. [ a halide ion, and, thus, we approach the convergence of borane and supramolecular chemistries.…”

Section: -mentioning

confidence: 99%

Icosahedral Building Blocks: Towards Dendrimers with Twelve Primary Branches?

Housecroft

1999

Angew. Chem. Int. Ed.

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A convergent point for cluster and supramolecular chemists is provided by the isolation of the per-B-hydroxylated, icosahedral clusters [B(12)(OH)(12)](2-) (shown schematically), [1-H-1-CB(11)(OH)(11)](-), and 1,12-H(2)-1,12-C(2)B(10)(OH)(10) by Hawthorne et al. But will these multifunctionalized clusters, which contain rigid cores and which can be supplied with "arms" in sterically favorable directions, be suitable building blocks for dendrimers?

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Preparation of C-2-pyridyl derivatives of icosahedral carboranes via copper(I) intermediates

Cited by 32 publications

References 23 publications

Carboranyl Derivatives of Rofecoxib with Cytostatic Activity against Human Melanoma and Colon Cancer Cells

Carboranyl Derivatives of Rofecoxib with Cytostatic Activity against Human Melanoma and Colon Cancer Cells

Four Decades of Organic Chemistry of closo-Boranes: A Synthetic Toolbox for Constructing Liquid Crystal Materials. A Review

Icosahedral Building Blocks: Towards Dendrimers with Twelve Primary Branches?

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